"As I'm sure you have, I have been reading report after report regarding these patients and trying to find some understanding of the pathophysiology that might help in treatment. A very interesting point was related to the possibility that the virus might actually bind to one of the hemoglobin subunits which might explain the severe hypoxia, but lack of symptoms. Many of us have seen patients walking around with just slight shortness of breath, but when checked, their oxygenation is in the low 80s, and they decompensate quickly with any minimal exertion. A physician in a COVID online group suggests an interaction with hemoglobin (HGB
), paraphrased as follows:HGB
has four cooperative binding sites. The sigmoid oxygen dissocation curve reflects the cumulative cooperativity among the sites. If the virus binds the beta-1 subunit, the curve shifts so that less oxygen is delivered to the tissue. The binding could actually change the shape of the curve. So do not let your patients walk to the bathroom and increase their oxygen requirement.

This was new to me, so I ran it by my friend, colleague, and RBC
metabolism expert Kathryn Doug, PhD, Michigan State University who then contacted her colleague, Rosemarie Brichta. Brichta located a rigorously scientific pre-pub manuscript, Liu W, Ki H, COVID-19 attacks the 1-beta chain of hemoglobin and captures the porphyrin to inhibit human heme metabolism. The article elegantly demonstrates how envelope proteins of the virus may bind homologous strands in porphyrin, the iron-bearing compound at
the center of the heme O2 pocket. Liu is from the School of Computer Science and Engineering, Sichuan University of Science & Engineering, Zigong, and Li from the School of Life Science and Food Engineering, Yibin University, Yibin, China. I will hope to post this article upon publication.

This post is an attempt to learn if others are seeing these distinctive symptoms, and if hydroxychloroquine, thought [unproven] to provide a measure of safety, somehow interferes with the Covid-porphyrin interaction.

"As I'm sure you have, I have been reading report after report regarding these patients and trying to find some understanding of the pathophysiology that might help in treatment. A very interesting point was related to the possibility that the virus might actually bind to one of the hemoglobin subunits which might explain the severe hypoxia, but lack of symptoms. Many of us have seen patients walking around with just slight shortness of breath, but when checked, their oxygenation is in the low 80s, and they decompensate quickly with any minimal exertion. A physician in a COVID online group suggests an interaction with hemoglobin (HGB
), paraphrased as follows:HGB
has four cooperative binding sites. The sigmoid oxygen dissocation curve reflects the cumulative cooperativity among the sites. If the virus binds the beta-1 subunit, the curve shifts so that less oxygen is delivered to the tissue. The binding could actually change the shape of the curve. So do not let your patients walk to the bathroom and increase their oxygen requirement.

This was new to me, so I ran it by my friend, colleague, and RBC
metabolism expert Kathryn Doug, PhD, Michigan State University who then contacted her colleague, Rosemarie Brichta. Brichta located a rigorously scientific pre-pub manuscript, Liu W, Ki H, COVID-19 attacks the 1-beta chain of hemoglobin and captures the porphyrin to inhibit human heme metabolism. The article elegantly demonstrates how envelope proteins of the virus may bind homologous strands in porphyrin, the iron-bearing compound at
the center of the heme O2 pocket. Liu is from the School of Computer Science and Engineering, Sichuan University of Science & Engineering, Zigong, and Li from the School of Life Science and Food Engineering, Yibin University, Yibin, China. I will hope to post this article upon publication.

This post is an attempt to learn if others are seeing these distinctive symptoms, and if hydroxychloroquine, thought [unproven] to provide a measure of safety, somehow interferes with the Covid-porphyrin interaction.

Hi George, I cannot speak on this topic per se, as my expertise does not stretch to hemoglobin structure. However, I will make a few comments. First, most of us in the thrombosis/hemostasis space do not normally think about viruses or other pathogens as causing T/H issues, although we do recognize general risks around sepsis for example. I will also raise as another example that viruses are known to bind and interact with platelets . We are publishing a state-of-the-art manuscript on this in Seminars in Thrombosis and Haemostasis--freely available--currently on eFirst online: . Of course, we do not know how (SARS-CoV-2)--the virus that causes COVID-19--interacts with platelets, but the precedent is there. Does SARS-CoV-2 bind to platelets and cause platelet activation? Or does platelet activation occur indirectly through other mechanisms post SARS-CoV-2 infection? Is platelet activation a feature of COVID-19? If so, does this then contribute to the associated reduction in platelet counts through clearance mechanisms separate to DIC related events? All excellent questions for clarification by those working on SARS-CoV-2/COVID-19 in the T/H space. I will also advise your readers that STH is also planning to publish a series of commentaries on SARS-CoV-2/COVID-19 in the T/H space over coming months. The first such commentary is online. This one is on: "Recommendations for Minimal Laboratory Testing Panels in Patients with COVID-19: Potential for Prognostic Monitoring." and is also just posted to eFirst: These commentaries will also be made free to download for readers. Finally, Thieme, the publisher of STH has created a Coronavirus Resource Center (https://www.thieme.com/resources/1721-coronavirus) where all SARS-CoV-2/COVID-19 material published by Thieme is planned to be posted for the foreseeable future - again free access.